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Depression: Is brain inflammation tied to suicidal thoughts?

A new study confirms the link between inflammation of the brain and the prevalence of suicidal thoughts in people diagnosed with major depression. This is the first study of its kind to measure relevant biomarkers in living individuals.

Researchers point to brain inflammation as a possible factor in suicidal ideation.

Major depression is a very common mental condition, with 6.7 percent of all adults in the United States having had at least one severe depressive episode in 2014 or 2015.

According to the World Health Organization (WHO), depression is also currently the leading cause of years spent with disability worldwide.

Some people diagnosed with major depression experience suicidal thoughts, which may result in suicide attempts. In the U.S., "suicide is the 10th leading cause of death." Now, researchers wonder whether or not suicidal ideation in people with major depression may be linked to abnormal inflammation of the brain.

Dr. Peter Talbot and other researchers based at the University of Manchester in the United Kingdom have conducted a study testing the levels of a biomarker associated with brain inflammation in the systems of people diagnosed with clinical depression.

The scientists' findings were reported in the journal Biological Psychiatry.

"This paper is an important addition to the view that inflammation is a feature of the neurobiology of a subgroup of depressed patients [...] with suicidal ideation," says journal editor Dr. John Krystal.

"This observation," he continues, "is particularly important in light of recent evidence supporting a personalized medicine approach to depression, i.e., that anti-inflammatory drugs may have antidepressant effects that are limited to patients with demonstrable inflammation."

Microglial activation 'prominent' in suicidality

Dr. Talbot and colleagues measured the levels of translocator protein (TSPO) in the brains of people diagnosed with major depressive disorder. TSPO generally plays a role in the immune response system and cell death.

In the brain, elevated TSPO levels activate the microglia, which are immune cells specific to this organ. Microglial activation indicates brain inflammation, so this is what the scientists targeted.

They worked with 14 people with moderate or severe depression not using antidepressants. Positron emission tomography was used to scan the participants' brains and identify signs of inflammation.

People with depression who were experiencing suicidal thoughts were found to exhibit significantly higher levels of TSPO, associated with microglial activation and indicating inflammation of the brain.

This, the researchers explain, suggests that inflammation is linked specifically with suicidal ideation, and not with depression more generally.

This is the first time that this link has been confirmed in living individuals. Previous studies, the researchers say, have had similar findings, but they only looked at brain tissue extracted after death.

"Our findings are the first results in living depressed patients to suggest that this microglial activation is most prominent in those with suicidal thinking," Dr. Talbot says.

Where inflammation of the brain was noted, it was usually in a region called the anterior cingulate cortex, which is involved with cognition and emotional processes. This supports previous findings that linked this brain region with depression and aspects of other mood disorders.

Signs of inflammation were also noted, albeit to a smaller degree, in the insula (or insular cortex), which plays a role in regulating emotional function, and in the prefrontal cortex, implicated in cognitive processes related to behavior.

Dr. Talbot explains that another study published in 2015 - by Dr. Elaine Setiawan, from the University of Toronto in Canada, and her colleagues - revealed similar links between brain inflammation and severe depressive events.

"The field now has two independent reports - our study and a 2015 report by Setiawan and colleagues in Toronto - showing essentially the same thing: that there is evidence for inflammation, more specifically microglial activation, in the brains of living patients during a major depressive episode."

Dr. Peter Talbot

He adds that the results of the current study warrant "further research into the question of whether novel treatments that reduce microglial activation may be effective in major depression and suicidality."

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